Ethanol → tert-Butyl 4-(4-(6-bromo-7-(4-(thiazol-4-ylmethyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazine-1-carboxylate

HRID 416942Notes

Reaction equation

HRID 416942 reaction equation
[Br:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[N:20]=[CH:21][S:22][CH:23]=3)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.CCO.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([CH:47]=O)=[CH:43][CH:42]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)Cl.N.CN(C=O)C>[Br:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[N:20]=[CH:21][S:22][CH:23]=3)[CH2:14][CH2:13]2)=[C:4]2[N:9]=[C:47]([C:44]3[CH:43]=[CH:42][C:41]([CH2:40][N:37]4[CH2:36][CH2:35][N:34]([C:32]([O:31][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:33])[CH2:39][CH2:38]4)=[CH:46][CH:45]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 24489Sodium DithioniteHCID 2795517tert-Butyl 4-(4-formylbenzyl)piperazine-1-carboxylateHCID 468667835-Bromo-3-nitro-4-(4-(thiazol-4-ylmethyl)piperazin-1-yl)pyridin-2-amine

Product 1

HCID 178452297tert-Butyl 4-(4-(6-bromo-7-(4-(thiazol-4-ylmethyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)benzyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 222AmmoniaCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of 5-bromo-3-nitro-4-(4-(thiazol-4-ylmethyl)piperazin-1-yl)pyridin-2-amine (0.054 g, 0.13 mmol), EtOH (2.3 mL) and DMF (0.31 mL), tert-butyl-4-(4-formylbenzyl)piperazine-1-carboxylate (0.045 g, 0.15 mmol, 1.1 eq) was added followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.40 mL, 0.40 mmol). The reaction mixture was heated at 85° C. for 24 h, then allowed to cool to room temperature and diluted with DCM and a few drops of aqueous NH3 until complete dissolution was observed. This solution was deposited on two preparative silica TLC plates and eluted with DCM/MeOH (v/v; 92:8). The title compound was obtained as a solid after trituration with diethyl ether (0.031 g, 35%); 1H-NMR (500 Mz, DMSO-d6): δ 1.39 (s, 9H, C(CH3)3), 2.34 (t, J=4.8 Hz, 4H), 2.65-2.72 (m, 4H), 3.30-3.36 (m, 4H), 3.55 (s, 2H, NCH2), 3.68 (m, 4H), 3.77 (s, 2H, NCH2), 7.47 (d, J=8.0 Hz, 2H, ArH, C6H4), 7.58 (d, J=2.0 Hz, 1H, thiazole 5-H), 8.14 (d, J=8.5 Hz, 2H, ArH, C6H4), 8.23 (s, 1H, imidazo[4,5-b]pyridine 5-H), 9.07 (d, J=2.0 Hz, 1H, thiazole 2-H), 13.47 (br s, 1H, imidazo[4,5-b]pyridine N—H); LC (method B)-MS (ESI, m/z) 2.50 min—653/655 [(M+H)+], Br isotopic pattern]. ESI-HRMS: Found: 653.2023, calculated for C30H38BrN8O2S (M+H)+: 653.2022.

Workup

  1. additionwas added
  2. temperatureto cool to room temperature
  3. washeluted with DCM/MeOH (v/v; 92:8)

Sources & evidence

ORD record
ord-b58b68e7f66747268b0c67c9e190cf00
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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